Can Paxlovid Relieve Long COVID Symptoms? For Some, Yes

Research on long COVID patients who took an extended course of Paxlovid shows mixed results.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

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• 1:29Ira Flatow?

  This is Science Friday. I'm Ira Flatow. Today on the podcast, could an antiviral treatment for COVID-19 also help people who've lived with long COVID for years?

• 1:40Speaker 03

  People living with long COVID are eager for treatments that can help with their symptoms, right? As you mentioned, we're about five years into this pandemic, and there are still not yet any FDA-approved treatments.

• 1:53Ira Flatow?

  Can you believe it's been five years since the first laboratory confirmed case of COVID-19 in the US? Of course, that pandemic has changed all of our lives, but for the lucky ones, only in small ways. For others, COVID-19 turned them into COVID long haulers. This is a chronic condition that lingers long after a COVID infection and can reduce one's ability to live their day-to-day life. It's been estimated that about 400 million people worldwide, yes, have had long COVID, and some researchers say that number should be much higher. There's a lack of research on successful treatments for long COVID.

• 2:35Ira Flatow?

  So some scientists living with the condition have taken things into their own hands, running experiments on themselves, and joining me to talk about a recent investigation using Paxlovid are my guests, Dr. Alison Cohen, Assistant Professor of Epidemiology and Biostatistics at the University of California in San Francisco, and Dr. Julia Moore Vogel, Senior Program Director at Scripps Research in La Jolla, California. Welcome both of you to Science Friday.

• 3:04Speaker 03

  Thank you so much.

• 3:05Speaker 04

  Thanks for having us.

• 3:06Ira Flatow?

  You're welcome. Before we just jump in, I want us to get to know you two a little better. So tell us a little bit about your research background and your experience, please, with long COVID. Alison, why don't you go first?

• 3:19Speaker 03

  Sure. So I'm an epidemiologist, and before the pandemic, a lot of people had never heard of epidemiology. Now more have. That means that I study patterns of health and well-being and apply that knowledge to try to improve public health. And in particular, I've built a career around doing what's called community-based participatory research, which means that I usually work in partnership with folks who are affected by different health issues to design and conduct rigorous research that can answer the health questions that are of highest priority to them. So in the last five years, that's included a lot of research related to COVID-19 pandemic and to long COVID. I've also been living with long COVID for the last three-plus years.

• 4:00Ira Flatow?

  What's that like?

• 4:01Speaker 03

  You know, there are... Over 200 different symptoms that folks with long COVID might have. So the experience of any given individual with long COVID may look pretty different. They can include symptoms like dysautonomia. And so that can affect circulatory system, things like orthostatic intolerance, which just makes it harder to be upright and get enough blood going to all of the different parts of your body. It can also affect fatigue. And so those are some of my primary symptoms.

• 4:38Ira Flatow?

  Right. And Julia, what's your experience with science and long COVID?

• 4:43Speaker 04

  Sure. So I'm a computational biologist by training. That means we take math, computer science and biology together to analyze data. And after getting my PhD, I went to get an MBA. And my idea was to sort of work at the interface of science and business. I've been doing that at Scripps Research for the past seven years, leading direct to participant, remote health research and clinical trials. My experience with long COVID started in July of 2020. I had a pretty typical acute case where I had the difficulty breathing and the fever and all of that. And I just never got better, which is wild, four and a half years later. And for me, one of the most difficult aspects is that it's actually gotten worse year over year, and it just feels completely out of my control.

• 5:27Speaker 04

  The main symptoms for me are fatigue in the physical sense. I now use a manual wheelchair with a power assist in the house. And I don't know if people are familiar with that sort of wheelchair, but it's basically like an e-bike, except a wheelchair version. But I used to be a long distance runner, super active. I could work as much as I wanted, only limited by the need to sleep eventually. And now I have to be very careful about how much I work. Or I trigger post exertional malaise, where my symptoms are just much worse for quite a while.

• 5:56Ira Flatow?

  So you two, you published in the journal Communications Medicine, a paper that you reported using Paxlovid to treat long COVID, right? I mean, I took Paxlovid when I got COVID for five days because I was in the high-risk category, but you used it for much longer, right, Allison? Tell us what the normal way to use it and what you guys did.

• 6:21Speaker 03

  Sure. So, most of your listeners might be familiar with Paxlovid as something that is taken in the acute stage, right after a known infection of COVID-19 has begun, and taking a five-day course. There have now been some studies in progress and/or recently completed that have been doing clinical trials to look at extended courses of Paxlovid outside of the context of a particular infection to see if that helps people with long COVID. People living with long COVID are eager for treatments that can help with their symptoms, right? As you mentioned, we're about five years into this pandemic

• 7:04Speaker 03

  and there are still not yet any FDA-approved treatments for long COVID. And the pace of clinical trial research can be slow. So, some patients have been trying different medications themselves. And so, we were just starting to hear about individuals' anecdotal experiences trying extended courses of Paxlovid. And then, with my epidemiologist hat on, it seemed like that could be helpful for both the scientific evidence base and patient knowledge to systematically document these experiences. So, what this paper did is talk with individuals with long COVID who had already tried extended courses of Paxlovid.

• 7:48Speaker 03

  So, we were typically talking with them after the fact and hearing about their experiences, all of their symptoms related to long COVID, both before, during, and after attempting this extended course of Paxlovid.

• 8:05Ira Flatow?

  Did it help people?

• 8:07Speaker 03

  Yeah, so we found that some patients reported a meaningful sustained improvement in their symptoms. Others had no improvements or only temporary improvements. And so, now the big question is, who may benefit from an extended course of Paxlovid and why? But our evidence does suggest that it might be helpful to at least some folks.

• 8:28Ira Flatow?

  Julia, you were not only a contributor on this paper, but you were one of the research participants. What was your experience with using this extended dose of Paxlovid?

• 8:40Speaker 04

  Yeah, unfortunately, I was one of the ones that it had no effect for. And this was not uncommon in the group. But there could be a lot of different reasons for this that really need to be explored and further research. One idea is the dosing. My physician advised me to take half the doses. So instead of taking it twice a day, I was taking it once a day over a longer period of time. That was their strategy. But it could be that, you know, a higher dose and maybe also over a longer period of time might be better. We're still not sure whether it crosses the blood brain barrier. There's been some studies in rats, but not in humans yet to confirm whether the drug can get into the brain, which is where a lot of the symptoms are hypothesized to manifest. And we know from autopsy studies that the virus does make it into the brain. And then the third

• 9:23Speaker 04

  piece is there's also a possibility of viral reactivation. So some people with long COVID not only have potentially issues with viral reservoirs of COVID, but also other viruses that are already in their body reactivating. So I've been confirmed to have them in a research study. And so it's possible that if those are the things driving my symptoms, then Paxlovid wouldn't be able to alleviate my symptoms. So all of this really points to the need for more subgroup analyses. That's part of what we're advocating for at this point, especially in the other trials, looking at Paxlovid and trying to understand whether it's working or not for folks. And this could include things like measuring viral persistence, you know, explicitly from people's blood and tissue, and looking at other things that

• 10:05Speaker 04

  are happening in their samples to try to stratify the people that do respond and don't respond.

• 10:11Ira Flatow?

  So Julia, it's possible there is no one silver bullet because of the mixed bag of results you got here for treating long COVID.

• 10:18Speaker 04

  Absolutely. I don't expect to have a silver bullet, just because, as Alison mentioned, there are over 200 different symptoms that can appear in any different combination. And then the other piece about it is there are about six different mechanisms of what can be causing long COVID. So everyone has in common COVID as the thing that started their long COVID. However, there are so many different physiological things going wrong in different people with long COVID, they might require different treatments.

• 10:44Ira Flatow?

  We have to take a break, and when we come back, we'll look at other trials going on to find a treatment for long COVID.

• 10:51Speaker 04

  So I mean, for me, I would like to see something like what we see in cancer, where there's just hundreds of trials going on.

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• 12:31Ira Flatow?

  You are both part of the Patient-Led Research Collaborative, Allison. Can you tell me about this?

• 12:36Speaker 03

  Sure. So the Patient-Led Research Collaborative is a group of researchers and other folks in the scientific arena who also have lived experience with long COVID. It was co-founded by folks who were part of that initial first wave of people to have long COVID. And then Julia and I have joined it more recently.

• 13:04Ira Flatow?

  Allison, to me, it seems like it would be an incredibly frustrating position to be in where you have this background in scientific research, you want there to be more research into this thing you're living with, and the research just isn't there. So you have to do it yourself. What's it like to be in that position?

• 13:26Speaker 03

  Yeah, it's a challenge. It's also a responsibility. It also feels like a worthwhile undertaking to have this deep empathy for what folks with long COVID are going through, as well as having all of these epidemiology textbooks on my bookshelf and all of that knowledge in my head in terms of thinking about, okay, how can we work at this nexus to do studies that are going to be rigorous and trusted

• 14:06Speaker 03

  by scientists around the world, and also research that is going to be trusted by patients all around the world and is going to be doing work that's useful for them. And given that so much of my background has been in doing epidemiologic research that is trying to directly answer questions that folks affected by certain health issues are experiencing, it was an honor that the 13 patients who were included in this case study

• 14:44Speaker 03

  trusted us with their time and their stories. And in doing this study in the first place, because of our own deep understanding, most of the authors involved in this paper have long COVID, there is a strong accountability that we have to this patient community.

• 15:06Ira Flatow?

  What about any frustration? Here, we're talking about the treatment side and basically throwing something on the wall and see if it sticks, right? What about the basic research to find out what causes long COVID? Is there frustration there too, Julia?

• 15:25Speaker 04

  I actually think we've made amazing progress as a field on the basic science side. Given how short it has been from the disease starting, five years in research time is not that much for how much we've learned. And my frustration is mainly at this point on the lack of trials because I think we know enough about the mechanisms of long COVID to turn the large majority of our attention to actually trying to treat it. And I know that that sense of urgency comes from my personal experience, right? You know, I have a young child and I know every year that goes by, I am missing a lot of things in her life because of my energy limitations. And so I want to get this done ASAP. So that definitely affects how I think about the long-term basic science research that

• 16:06Speaker 04

  takes quite a while to deliver versus a trial that we could run today and have results on, you know, within a year.

• 16:13Ira Flatow?

  You know, when a trial, you're talking about Paxlovid in a larger scale.

• 16:17Speaker 04

  Oh, no, I mean, all clinical trials. I think that the field should be more focused on clinical trials than it is right now.

• 16:23Ira Flatow?

  Of what? Do we have drugs that you're thinking of?

• 16:25Speaker 04

  Yes, well, so there are actually a lot of great trials going on. This is the first year that I'm excited about the slate of trials that are happening. So I can definitely list a number of them. So one looking at mitochondrial dysfunction is rapamycin, which David Petrino's group is running. And the reason that I personally feel that mitochondrial dysfunction resonates with me and how I feel physiologically, that there is just no energy to be had. I can't just push through the way I would have as a long-distance runner, you know, in mile 10 of my jog. There's just nothing. So I'm really excited about something to treat mitochondrial dysfunction. There's a few looking at immunomodulation with JAK inhibitors, both the bear sitinib

• 17:08Speaker 04

  trial by Wes Eli's group and another JAK inhibitor trial that's starting at Harvard. Another immunomodulation option is IVIG, which is being run by the NIH Recover Consortium. This one's tricky because it's not super scalable. You have to get the antibodies from people and then infuse them into other people. So it's a, it's, it would be a difficult thing to scale, but it's very interesting to see, you know, what's going to happen for folks. And then the other Mechanism that's being looked at a lot now is viral persistence, both through a few different monoclonal antibodies trials. Michael Peluso's funded by the Patient Led Research Collaborative. Nancy Klimas is just starting one funded by the Schmidt Initiative for Long COVID and the state of California.

• 17:52Speaker 04

  And then there's another one in Italy that's funded by industry, all looking at monoclonal antibodies. And then the last viral persistence one is also being run by the Petrino Group on Truvata, which is an HIV antiviral.

• 18:04Ira Flatow?

  You're saying there's no dearth of trials going on?

• 18:07Speaker 04

  Well, I think we are finally getting to start some trials now. However, as we mentioned before, there's going to be different things that work for different people. So we need a very large array of trials. And not all of these trials are well powered enough that we would, at the end of the day, be able to say, okay, we can now give this drug to everyone with long COVID. So many of them are underfunded that they're, you know, like a 40 person trial, which you can't make a treatment decision for millions of people based on. So there really needs to be more funding going into these studies. You know, hopefully from industry, philanthropy, NIH will take everything we can get. And then the other piece that I haven't seen as much in terms of the trials

• 18:50Speaker 04

  is there are probably a lot of generics on the shelf that we could look into. However, industry isn't incentivized to doing those trials. So we really need other funding sources to be able to get those going. So, I mean, for me, I would like to see something like what we see in cancer, where there's just hundreds of trials going on, right? Because just like cancer, there are a disparate array of things happening in long COVID. And we are going to need a whole portfolio of drugs to be able to solve it for the entire community.

• 19:19Ira Flatow?

  One last question for you, Julia. We're entering a political administration that has demonstrated sort of a lack of interest in some areas of basic research and scientific research. Is that, do you have any fears about the future of long COVID here?

• 19:35Speaker 04

  I definitely have some fears about the future of what might happen. I would really ask the administration to think about prioritizing the Long COVID Research Moonshot Act that's been introduced in Congress, which is aiming to provide a billion dollars a year of funding over the next 10 years to solve this crisis. I think that it is not the time to take a pause on infectious disease research. You know, long COVID aside, seeing the H5N1 cases looming, I think there's a lot to be done in this space, and I hope that we can continue to invest in things that are good for the public as a whole and continue to maintain, you know, our nation's reputation as a leader in science and medicine.

• 20:20Ira Flatow?

  Well, with that, I want to thank both of you for taking time to be with us today. We've run out of time. Dr. Allison Cohen, Assistant Professor of Epidemiology and Biostatistics at UC San Francisco, Dr. Julia Moore Vogel, Senior Program Director at Scripps Research in La Jolla, California. Thank you both, and good luck to both of you.

• 20:39Speaker 04

  Thanks for having us.

• 20:40Speaker 03

  Thank you so much.

• 20:46Ira Flatow?

  That's about all the time we have for now. A lot of people helped make this show happen. John Dankoski. Kathleen Davis. Steve Peterschmidt. Robin Casmer. I'm Ira Flatow. Thanks for listening.